There is ample evidence to indicate that erythroid maturation is impaired in patients with sideroblastic anemias. Mitochondrial iron accumulation, nucleic acid synthesis, heme synthesis, etc. have been linked to the impaired maturation sequence of this anemia. Evaluation of factors contributing to this process will be studied in laboratory animals in which sideroblastic anemia has been induced by those agents linked to its development in humans. The studies in mice are designed to detect abnormalities of erythropoietic flow characteristics induced by these agents. Lead, for example, when tested in this system, was found to interfere with the maturation of intermediate normoblasts without appreciably affecting the committee erythroid stem cell. pronormoblast, or late normoblast. Sideroblastic anemia or comparable defects in the iron incorporation--heme synthesis pathway will be induced by lead and isoniazid. A heme biosynthetic defect in mice with erythroleukemia will also be evaluated. Ferrokinetics, cell cycle kinetics of erythroid precursors, and heme biosynthesis represent the major parameters to be assessed. In vitro measurements of heme synthesis from the marrow and blood of patients with erythroleukemia and sideroblastic anemias should tend to enhance the clinical importance of the observations and provide better insight into those diseases in man in which there are abnormalities in cell proliferation.